Severe delayed pulmonary toxicity following PD-L1-specific CAR-T cell therapy for non-small cell lung cancer

This phase I study aimed to evaluate the antitumor effect and safety of programmed death-ligand-1 (PD-L1)-targeting autologous chimeric antigen receptor T (CAR-T) cells for patients with non-small cell lung cancer (NSCLC).

Programmed death-ligand-1-specific CAR-T cells were generated using lentiviral transduction. Four patients with NSCLC were recruited, but only one patient was finally involved. CAR-T cells were infused on three different days (total dose during therapy, 1 × 10⁶ CAR-T cells kg^-1 body weight). The date on which the patient received the first CAR-T cell infusion was designated as Day 0.

Circulating CAR-T cells accounted for 3.30% of the patient's peripheral blood T cells detected by FACS analysis during the first follow-up (Day +29). The chest CT scan showed subtle tumor shrinkage (stable disease). On Day +43, the patient developed pyrexia without any known causes and dyspnoea that rapidly deteriorated to respiratory failure in 3 days. The chest X-ray and CT scan showed bilateral extensive pulmonary infiltration in addition to the tumor silhouette on the left upper lung. The interleukin (IL)-6 levels in serum dramatically increased (> 100-fold). The patient was immediately transferred to the ICU where he received oxygen and intravenous infusions of tocilizumab and methylprednisolone. His symptoms rapidly improved and the pulmonary inflammation gradually resolved.

The clinical manifestations and test findings for this patient with NSCLC might represent unique clinical manifestations of solitary organ damage secondary to PD-L1-specific CAR-T cell therapy. The differential diagnosis, underlying mechanism and prevention and treatment strategies for such complications have also been discussed.